DESCRIPTION: The objective of the proposed research is to gain a fundamental structural, spectroscopic, and mechanistic chemical understanding of copper protein active sites of biological and environmental importance through the synthesis, characterization, and examination of the reactivity of model complexes. Through this approach the principles that control the structures and functions of central enzymes in the biological nitrogen cycle (nitrite and nitrous oxide reductase), proteins that bind or reduce oxygen during metabolic processes (hemocyanin, cytochrome oxidase), and enzymes that functionalize organic substrates to provide important metabolites (tyrosinase, dopamine beta-monooxygenase, peptidyl glycine amidating enzyme, particulate methane monooxygenase, and galactose oxidase) will be revealed. Although structurally and functionally diverse. these biomolecules follow reaction paths that have in common key chemical steps involving the binding and/or activation of dioxygen or nitrogen oxides. small molecules whose consumption and generation in nature is critically important for the functioning of life. The specific alms of the proposed research are to understand in detail the structures of the active sites of the proteins that interact with dioxygen and various nitrogen oxides and to unravel how these small molecules are activated during, enzymatic processes. In particular. a divergent set of ligands that nonetheless have in common a specific N-donor framework will be used to construct unique copper complexes designed to mimic key aspects of the protein active sites. These complexes will be fully characterized by structural, spectroscopic, and. in some instances. theoretical methods in order to draw comparisons to the biological systems. Parallel studies of the mechanisms of biomimetic reactions of these complexes will be performed in order to understand structure/function relationships. Emphasis during these modeling studies will be placed on addressing the following issues (i) the properties of copper protein- dioxygen adducts and the pathways by which the dioxygen O-O bond is cleaved and substrates are oxidized. (ii) the influence of secondary hydrogen-bonding interactions on copper-dioxygen and -nitrogen oxide adduct structure and reactivity. (iii) structure/function relationships for the unusual dithiolate-bridged. mixed valent. dicopper "Cu-a," electron transfer site present in cytochrome oxidase and nitrous oxide reductase. (iv) the structural, spectroscopic features, and reactivity of copper-organic radical arrays in proteins. and (v) the scope and mechanism of NO release by new copper complexes of some higher-order nitrogen oxides that may have pharmacological applications. ultimately, the combined synthetic, physicochemical. and mechanistic studies that we propose will contribute toward the elucidation of the fundamental chemical principles that underlie copper protein structure and function. with additional potential for discovery of new catalysts or reagents.